LRX-1 is a poorly characterized cysteine-rich protein of unknown function in C. elegans. It is a 368-residue protein with a predicted N-terminal signal peptide and, in its C-terminal half, four low-density lipoprotein receptor class A (LDL-A) repeats, recognized by Pfam, SMART, PROSITE and CDD, and it falls in the LDL receptor-related PANTHER family (EGG-1-related subfamily). Despite its name ("LRP cross-hybridizing") it is not a member of the large LRP receptor family, since it lacks the EGF-like repeats and beta-propeller domains of those receptors and is about ten times smaller. No transmembrane segment is predicted after the last LDL-A repeat, which ends at the C terminus, so LRX-1 is probably secreted. High-throughput screens identified interactions with RSP-4, PFD-3, and PERM-4 (eggshell integrity protein), suggesting potential involvement in extracellular matrix organization, though biological significance remains unclear.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0012505 endomembrane system | IEA GO_REF:0000044 | REMOVE | Summary: ARBA-based prediction without experimental support Reason: Based on incorrect membrane protein prediction; bioinformatic analysis suggests secreted protein, not membrane-bound. Falcon deep research independently found no experimental evidence for any subcellular localization of lrx-1. Supporting Evidence: file:worm/lrx-1/lrx-1-deep-research-falcon.md direct primary experimental characterization of lrx-1/T04H1.6 (loss-of-function phenotypes, biochemical activity, or cellular localization) was not found |
| GO:0016020 membrane | IEA GO_REF:0000120 | REMOVE | Summary: ARBA-based prediction of membrane localization Reason: No strong transmembrane helix detected; weak hydrophobic regions incompatible with membrane insertion. Falcon deep research found no experimental localization data and states membrane/secreted assignment cannot be made beyond domain-based inference. Supporting Evidence: file:worm/lrx-1/lrx-1-deep-research-falcon.md Therefore, **primary function, substrate/ligand specificity, and site of action (tissue/subcellular)** cannot be stated beyond domain-based inference without overreach. file:worm/lrx-1/lrx-1-hypotheses/function-hypothesis-go-0016020/openscientist.md The GO:0016020 (membrane) annotation for *C. elegans* lrx-1 (UniProt Q22179) is **over-annotated** and should be removed. |
| GO:0016192 vesicle-mediated transport | IEA GO_REF:0000117 | REMOVE | Summary: ARBA-based prediction from the LDL receptor class A repeat signature Reason: The ARBA rule rests on LRX-1's LDL-A repeats, which are genuine (Pfam, SMART, PROSITE and CDD each detect four), but LDL-A repeats occur in many secreted and extracellular-matrix proteins and do not by themselves imply endocytic or vesicle transport. LRX-1 has no transmembrane segment or cytoplasmic internalization motif and no evidence for cargo receptor function. Falcon deep research explicitly states there is no evidence base to claim lrx-1 mediates endocytosis or binds lipoprotein ligands. Supporting Evidence: file:worm/lrx-1/lrx-1-deep-research-falcon.md Without direct lrx-1 experiments in the retrieved texts, it is not evidence-based to claim: - that lrx-1 binds cholesterol or specific lipoprotein ligands, - that it mediates endocytosis |
| GO:0003674 molecular_function | NAS | NEW | Summary: Added to align core_functions with existing annotations. The molecular function of LRX-1 is unknown; the previously proposed 'protein binding' (GO:0005515) term was uninformative and was not backed by any binding evidence for LRX-1, so the root molecular_function term is used instead to reflect genuine uncertainty. Reason: Per curation guidelines, 'protein binding' (GO:0005515) is uninformative and should be avoided. LRX-1 has four LDL-A repeats, which typically bind ligands, but no ligand is known, and Falcon deep research found no experimental evidence that lrx-1 binds any defined ligand or has any demonstrated molecular function. The high-throughput Y2H interactions are retained descriptively in the references but do not justify a specific MF annotation. Supporting Evidence: file:worm/lrx-1/lrx-1-deep-research-falcon.md Therefore, **primary function, substrate/ligand specificity, and site of action (tissue/subcellular)** cannot be stated beyond domain-based inference without overreach. |
| GO:0005576 extracellular region | IEA | NEW | Summary: Tentative extracellular/secreted localization inferred from sequence analysis (weak signal peptide, no transmembrane helix). Note that Falcon deep research found no experimental localization data, so this remains a prediction. Reason: Bioinformatic analysis predicts a secreted protein (weak N-terminal signal peptide, no transmembrane helix), favouring an extracellular localization over the removed membrane/endomembrane annotations. This is a sequence-based inference only; Falcon deep research explicitly states that the site of action cannot be established beyond domain-based inference, so the annotation is tentative. Supporting Evidence: file:worm/lrx-1/lrx-1-deep-research.md LRX-1 is a secreted, extracellular protein with a signal peptide directing it into the secretory pathway. It lacks transmembrane regions and is expected to reside in the extracellular matrix or periphery of cells file:worm/lrx-1/lrx-1-deep-research-falcon.md Therefore, **primary function, substrate/ligand specificity, and site of action (tissue/subcellular)** cannot be stated beyond domain-based inference without overreach. |
| GO:0009987 cellular process | NAS | NEW | Summary: Added to align core_functions with existing annotations. Reason: Core function term not present in existing_annotations. |
Loading supporting content…
Download this section (compressed HTML)Q: Is LRX-1 secreted, as its signal peptide and lack of a transmembrane segment predict, and where does the secreted protein accumulate (eggshell, extracellular matrix, pseudocoelom)?
Q: What do the four LDL-A repeats of LRX-1 bind? LDL-A modules in other proteins bind calcium and lipoprotein or protein ligands.
Q: Is the high-throughput interaction with the eggshell protein PERM-4 reproducible, and does LRX-1 contribute to eggshell integrity?
Experiment: Endogenous fluorescent tag of LRX-1 by CRISPR knock-in to test secretion and map its extracellular localization through development
Experiment: CRISPR null allele of lrx-1, tested for eggshell permeability and embryonic viability alongside perm-4 loss of function
Experiment: Recombinant LRX-1 LDL-A region, tested for calcium-dependent binding to candidate ligands and for direct binding to PERM-4
Loading supporting content…
Download this section (compressed HTML)lrx-1 encodes a protein that contains four class A low-density lipoprotein receptor domains.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)📊 View Pathway Visualization Interactive pathway diagram with detailed annotations